Vitrectomy with sulfur hexafluoride versus air tamponade for idiopathic macular hole: a retrospective study.

BACKGROUND: To evaluate the effect of room air and sulfur hexafluoride (SF6) gas in idiopathic macular hole(MH)surgery. METHODS: Retrospective, interventional, and comparative study. 238 eyes with the idiopathic macular hole that underwent pars plana vitrectomy, internal limiting membrane peeling, fluid-air exchange, and 20% SF6 (SF6 group:125 eyes) or room air tamponade (air group: 113 eyes) were reviewed. The primary outcome measure was the closure rate of primary surgery. RESULTS: The baseline characteristics of the SF6 group and air group were comparable except for the hole size (479.90 ± 204.48 vs. 429.38 ± 174.63 µm, P = 0.043). The anatomical closure rate was 92.8% (116 / 125) with the SF6 group and 76.1% (86 / 113) with the air group (P < 0.001). A cut-off value of MH size to predict primary anatomical closure was 520 µm, which is based on the lower limit of 95% confidential interval of the MH size among the unclosed patients in the air group. There was no significant difference in anatomical closure rates between SF6 and air group (98.7% vs. 91.9%, P = 0.051) for MH ≤ 520 µm, whereas a significantly lower anatomical closure rate was shown in the air group than SF6 group (46.2% vs. 84.0%, P < 0.001) for MH > 520 µm. CONCLUSION: SF6 exhibited more effectiveness than air to achieve a good anatomical outcome for its longer tamponade when MH > 520 µm.

Ionic Conductive and Highly-Stable Interface for Alkali Metal Anodes.

Alkali metals are regarded as the most promising candidates for advanced anode for the next-generation batteries due to their high specific capacity, low electrochemical potential, and lightweight. However, critical problems of the alkali metal anodes, especially dendrite formation and interface stabilization, remain challenging to overcome. The solid electrolyte interphase (SEI) is a key factor affecting Li and Na deposition behavior and electrochemical performances. Herein, a facile and universal approach is successfully developed to fabricate ionic conductive interfaces for Li and Na metal anodes by modified atomic layer deposition (ALD). In this process, the Li metal (or Na metal) plays the role of Li (or Na) source without any additional Li (or Na) precursor during ALD. Moreover, the key questions about the influence of ALD deposition temperature on the compositions and structure of the coatings are addressed. The optimized ionic conductive coatings have significantly improved the electrochemical performances. In addition, the electrochemical phase-field model is performed to prove that the ionic conductive coating is very effective in promoting uniform electrodeposition. This approach is universal and can be potentially applied to other different metal anodes. At the same time, it can be extended to other types of coatings or other deposition techniques.

Risk factors of persistent subretinal fluid after half-dose photodynamic therapy for treatment-naïve central serous chorioretinopathy.

PURPOSE: To investigate the prognostic factors on spectral domain optical coherence tomography (SD-OCT) associated with incomplete subretinal fluid (SRF) absorption in treated-naïve eyes with central serous chorioretinopathy (CSC) after the half-dose verteporfin photodynamic therapy (vPDT). METHODS: Patients with CSC who underwent half-dose vPDT with a follow-up period of more than 3 months were included in this retrospective study. Logistic regression was performed to determine the risk factors associated with the SRF persistence at 3 months after the treatment. RESULTS: A total of 143 patients with 150 eyes were enrolled in this study (102 male and 41 female patients). The rate of complete SRF resolution was 82.7% at 3 months for all cases. The duration of symptoms > 6 months (odds ratio [OR] = 3.135, 95% confidence interval [95% CI] (1.147-8.573), p = 0.026), larger SRF area with base diameter > 3 mm (odds ratio (OR) = 4.051, 95% CI: 1.336-12.284, p = 0.013), and larger flat irregular pigment epithelium detachment (FI-PED) area with base diameter > 1 mm (OR = 3.311, 95% CI: 1.249-8.780, p = 0.016) on OCT B-scans were risk factors for incomplete SRF absorption after half-dose vPDT, while outer nuclear layer (ONL) thickness was not significantly associated with the anatomical outcome (OR = 1.015, 95% CI: 0.995-1.036, p = 0.145). CONCLUSION: The duration of symptoms, baseline SRF, and FI-PED base diameter on SD-OCT were important predictors for the anatomical outcome at 3 months after half-dose vPDT. Further studies are needed to establish a better therapeutic strategy for patients with poor response to half-dose vPDT.

Plasma metabolomic profiling of central serous chorioretinopathy.

Our study aimed to investigate metabolites alterations in the blood plasma of central serous chorioretinopathy (CSC) patients and to identify the key biomarkers to increase the understanding of the mechanism of CSC at the molecular level. Quantitative and targeted metabolomics using liquid chromatography tandem-mass spectrometry (LCMS, Biocrates P500) assays were performed on plasma samples from the 42 subjects(CSC patients = 30, control = 12) enrolled at the Department of Ophthalmology of People's Hospital Peking University. A total of 61 altered metabolites were distinguished between CSC patients and controls. Taurine was selected as a candidate biomarker for CSC among 6 potential metobolites: taurine, glutamic acid, sarcosine, lactic acid, glutamine and C18_1. The P values of these potential metabolites were 1.01E-06, 7.35E-08, 1.27E-24, and 1.85E-10, 1.02E-05 and 8.59E-08, and the areas under the curve for them were 0.926, 0.991, 1.000, 0.900, 0.897 and 0.841, respectively. This study is the first to identify that taurine may be a biologically relevant biomarker for CSC and to provide a novel understanding of CSC.

SHORT-TERM OUTCOMES AFTER INTRAVITREAL INJECTIONS OF CONBERCEPT VERSUS RANIBIZUMAB FOR THE TREATMENT OF RETINOPATHY OF PREMATURITY.

PURPOSE: Intravitreal injection of conbercept (IVC) is the latest applied treatment that could be used in retinopathy of prematurity (ROP) patients. The structural outcomes and recurrence of ROP among patients treated with IVC or intravitreal injection of ranibizumab (IVR) were compared. METHODS: A consecutive case series of ROP treated with IVC or IVR were retrospectively studied. The primary outcome was treatment success defined as regression of plus disease. The secondary outcomes were recurrence of plus, times of injection, and the final regression of disease. RESULTS: A total of 48 eyes (24 patients) with ROP were included. Twenty eyes (10 patients) received IVC, and 28 eyes (14 patients) received IVR. For the IVC group, 18 eyes had Zone II 3+ ROP and 2 eyes had aggressive posterior ROP. Among the 28 eyes treated with IVR, 6 eyes had Zone I 2/3+ ROP, 6 eyes had aggressive posterior ROP, and 16 eyes had Zone II 3+ ROP. For the IVC group, the mean gestational age, birth weight, postmenstrual age at initial treatment, and follow-up period for the infants were 29.49 ± 1.37 weeks, 1,369.0 ± 161.9 g, 38.47 ± 2.72 weeks, and 52.6 ± 21.4 weeks, respectively. And for the infants who received IVR, these were 28.35 ± 1.62 weeks, 1,171.4 ± 279.9 g, 38.53 ± 3.54 weeks, and 42.9 ± 9.8 weeks, respectively. For the IVC group, 17 (85%) of 20 eyes received the injection only once, and the regression of plus disease occurred 4.3 ± 2.08 weeks later. Three eyes (15%) did not healed with one injection received a second IVC, and the regression of plus disease occurred within 3 weeks. For the IVR group, 15/28 (53.6%) eyes received a second IVR. Among them, 10 recurrent eyes and 5 eyes did not recover with one injection. No retinal detachment was observed in both group infants. CONCLUSION: Both conbercept and ranibizumab are effective choice for the treatment of ROP. Conbercept is a novel effective treatment strategy for ROP providing a new treatment option for ophthalmologists.

The repeatability of superficial retinal vessel density measurements in eyes with long axial length using optical coherence tomography angiography.

BACKGROUND: To investigate the repeatability of superficial retinal vessel density measurements in healthy eyes with long axial length (AL) using optical coherence tomography angiography (OCTA). METHODS: There were 60 eyes of 31 volunteers enrolled in this cross-sectional observational study. All subjects underwent OCTA, AL and refraction test. The enrolled eyes were divided into the long AL group (26 mm ≤ AL < 28 mm) and normal AL group (22 mm ≤ AL < 26 mm). The vessel length density (VLD), perfusion density (PD), and fovea avascular zone (FAZ) of the superficial retinal vessel were evaluated. Repeatability was assessed by intraclass correlation coefficients (ICCs) and Bland-Altman analysis. Pearson's r correlation was used to analyze the relation of AL and the absolute difference between two measurements. RESULTS: The 3 × 3 mm scan pattern showed good repeatability with all ICCs over 0.7. For all parameters of all scan patterns, the ICCs of the normal AL group were distinctly higher than those of the long AL group; this finding was also confirmed by Bland-Altman analysis. The correlation analysis of AL and repeatability of OCTA parameters showed significant negative correlations between the ALs and repeatability of VLD in 6 × 6 mm inner ring (r2 = 0.13, p = 0.01), VLD in 6 × 6 mm outer ring (r2 = 0.09, p = 0.02) and PD in 6 × 6 mm outer ring (r2 = 0.08, p = 0.03). CONCLUSIONS: The AL and the scanned area will both affect the repeatability of superficial retinal vessel density measurements in OCTA.

The effects of pleiotrophin in proliferative vitreoretinopathy.

PURPOSE: The purpose of our study was to investigate the effects of pleiotrophin (PTN) in proliferative vitreoretinopathy (PVR) both in vitro and in vivo. METHODS: Immunofluorescence was used to observe the PTN expression in periretinal membrane samples from patients with PVR and controls. ARPE-19 cells were exposed to TGF-ß1. The epithelial-to-mesenchymal transition (EMT) of the ARPE-19 cells was confirmed by observed morphological changes and the increased expression of α-SMA and fibronectin at both the mRNA and protein levels. We used specific small interfering (si)RNA to knock down the expression of PTN. The subsequent effects of PTN inhibition were assessed with regard to the EMT, migration, proliferation, cytoskeletal arrangement, TGF-ß signaling, PTN signaling, integral tight junction protein expression (e.g., claudin-1 and occludin), and p38 MAPK and p-p38 MAPK levels. Additionally, a PVR rat model was established by the intravitreal injection of ARPE-19 cells transfected with PTN-siRNA and was evaluated accordingly. RESULTS: PTN was highly expressed in PVR membranes compared to controls. PTN knockdown attenuated the TGF-ß1-induced migration, proliferation, cytoskeletal rearrangement, and expression of EMT markers such as α-SMA and fibronectin in the ARPE-19 cells, and these effects may have been mediated through p38 MAPK signaling pathway activation. PTN silencing inhibited the up-regulation of claudin-1 and occludin stimulated by TGF-ß1, and PTN knockdown inhibited the proliferative aspects of severe PVR in vivo. CONCLUSIONS: PTN is involved in the process of EMT induced by TGF-ß1 in human ARPE-19 cells in vitro, and PTN knockdown attenuated the progression of experimental PVR in vivo. These findings provide new insights into the pathogenesis of PVR.

SERUM LEVELS OF VASCULAR ENDOTHELIAL GROWTH FACTOR BEFORE AND AFTER INTRAVITREAL INJECTION OF RANIBIZUMAB OR CONBERCEPT FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

OBJECTIVE: To investigate the serum levels of vascular endothelial growth factor (VEGF) before and after intravitreal injection of conbercept or ranibizumab for neovascular age-related macular degeneration and polypoidal choroidal vasculopathy patients. METHODS: This study is a prospective, interventional case series and involved 28 patients, 18 treated with 0.5 mg of conbercept and 10 treated with 0.5 mg of ranibizumab. Serum concentrations of VEGF were determined by enzyme-linked immunosorbent assay before the injection and at 1 day, 1 week, and 1 month after anti-VEGF treatments. RESULTS: The baseline serum VEGF level of the ranibizumab group was 367.11 ± 311.87 pg/mL, whereas that of the conbercept group was 315.06 ± 170.88 pg/mL (P = 0.653). In the conbercept group, VEGF level significantly decreased to 36.32 ± 72.11 pg/mL at 1 day (P = 0.03) and returned to 136.55 ± 144.62 pg/mL at 1 week (P = 0.03). At 1 month, the concentration increased to 334.48 ± 197.41 pg/mL and showed no significant difference compared with the baseline. In the ranibizumab group, the serum VEGF levels were 292.42 ± 239.80 pg/mL, 282.60 ± 201.36 pg/mL, and 308.83 ± 266.89 pg/mL at 1 day, 1 week, and 1 month after intravitreal injection, respectively. There was no significant difference in the ranibizumab group at each detection time point (P = 0.45). CONCLUSION: Conbercept significantly decreased serum VEGF level 1 day and 1 week after injection, but this effect was not sustained for 1 month. In contrast, ranibizumab had no significant effect on serum VEGF concentration changes. The reduction in serum VEGF by conbercept may affect its systemic safety profile.

Sensitivity and specificity of multispectral imaging in detecting central serous chorioretinopathy.

BACKGROUND AND OBJECTIVE: Central serous chorioretinopathy (CSCR) is a common and idiopathic retinal disorder that affects young to middle aged adults. The aim of this study was to describe the characteristics of eyes with CSCR using a light-emitting diode (LED)-based multispectral imaging (MSI) system and to evaluate the diagnostic reliability of MSI compared to fluorescein angiography (FA) in detecting CSCR. MATERIALS AND METHODS: A total of 56 eyes among 52 patients with 1 or more retinal pigment epithelium (RPE) abnormality were retrospectively enrolled in the study. The patients underwent complete examination, including optical coherence tomography, FA, indocyanine-green angiography, and MSI. MSI images were retrospectively reviewed by experienced masked graders. Diagnoses that were made based on MSI alone were compared with those that were made using FA. Sensitivity and specificity were calculated, and the morphological features on MSI were summarized. RESULTS: Among 56 eyes in 52 patients, MSI detected 22 of 26 true-positive CSCR cases but missed 4 FA-confirmed lesions. Further, it correctly excluded 30 of 30 non-CSCR lesions. The sensitivity and specificity of MSI were 84.6 and 100%, respectively, for identifying CSCR. Using MSI, RPE leakage was observed in 25 (96.2%) of 26 eyes with CSCR, which was comparable to the performance of FA. Dome-shaped areas of signal, which corresponded to fluid accumulation associated with neurosensory retinal detachment or RPE detachment were observed in 23 (88.5%) of 26 eyes. CONCLUSIONS: As a non-invasive technique, MSI permitted the visualization of RPE leakage and neurosensory detachment and allowed good detection of CSCR in this selected clinical population. Lasers Surg. Med. 49:498-505, 2017. © 2016 Wiley Periodicals, Inc.

Comparative effectiveness of intravitreal bevacizumab with or without triamcinolone acetonide for treatment of diabetic macular edema.

BACKGROUND: Bevacizumab and triamcinolone acetonide (TA) are both common choices for treatment of diabetic macular edema (DME), but the comparative efficacy of combined or separate applications is still not determined. OBJECTIVES: To compare the treatment efficacy of intravitreal bevacizumab (IVB) and the combination of IVB and intravitreal triamcinolone (IVT) for DME patients. METHODS: PubMed, EMBASE, and the Cochrane library were systematically reviewed for randomized controlled trials comparing IVB with IVB/IVT. Data on visual acuity (VA) and central macular thickness (CMT) changes at 3 and 6 months were extracted and data on adverse events were collected. A meta-analysis was performed using the software RevMan 5.3. The methodological quality and bias risks were also evaluated. RESULTS: VA improved more significantly in the IVB/IVT group compared with the IVB group at 3 months (mean difference [MD] = 0.07; 95% CI = 0.01 to 0.13), whereas there was no significant difference at 6 months (MD = -0.01; 95%CI = -0.11 to 0.09). The CMT reduction in the IVB/IVT group was significantly greater than that in the IVB group at 3 months (MD = 48.40; 95%CI = 30.23 to 66.57), but no statistically significant difference was found at 6 months (MD = 0.47; 95%CI = -24.11 to 25.04). Ocular hypertension was detected in 9/243 eyes in the IVB/IVT group but none of the IVB eyes. CONCLUSION: IVB/IVT is more effective for improving VA and decreasing CMT at 3 months in DME. A single injection of TA along with the first IVB could improve outcome within 3 months, but this is not sustained at 6 months. Continuous IVT/IVB treatment should be performed in further trials to clarify its long-term potential efficacy.

[Macular thickness in unilateral amblyopia as measured by optical coherence tomography: a meta analysis].

OBJECTIVE: To offer a clue for the etiology of amblyopia by systematically comparing the macular thickness measured by optical coherence tomography (OCT) between the amblyopic eye and the fellow normal eye in patients with unilateral amblyopia. METHODS: Databases including Wanfang, PubMed and others were searched, and data were extracted after quality assessment, then the Meta analysis was performed by the RevMan 5.02 software. RESULTS: Four studies using the time-domain OCT (TD-OCT) were enrolled in the analysis and all those were anisometropic amblyopic patients. The only one study showed that the foveal minimum thickness is thicker in the amblyopic eyes than the fellow ones (P = 0.045). The meta analysis indicated the amblyopic eyes were 6.82 µm (P < 0.05, 95% CI: 2.81-10.83) thicker in the fovea (1 mm diameter region ). Five trials using the spectral-domain OCT (SD-OCT) were included in the analysis. It showed no significant difference in the foveal minimum thickness between amblyopic and fellow eyes. Also, no significant difference were detected in either anisometropic or strabismic subgroup (P = 0.50). Amblyopic eyes were 7.38 µm thicker in the fovea (1 mm diameter region) (P < 0.05, 95% CI: 3.13 -11.63) and significant difference in the anisometropic subgroup while no significant difference in the strabismic subgroup were detected. CONCLUSIONS: The macular fovea is thicker in the amblyopic eyes than the fellow ones by the use of OCT, so it is effective to measure the macular thickness of amblyopia in searching evidence for the etiology of amblyopia.

Electro-Chemo-Mechanically Stable and Sodiophilic Interface for Na Metal Anode in Liquid-based and Solid-State Batteries.

Na metal batteries (NMBs) are attracting increasing attention because of their high energy density. However, the widespread application of NMBs is hindered by the growth of Na dendrites and interface instability. The design of artificial solid electrolyte interphase (SEI) with tuned chemical/electrochemical/mechanical properties is the key to achieving high-performance NMBs. This work develops a metal-doped nanoscale polymeric film with tunable composition, sodiophilic sites and improved stiffness. The incorporation of metal crosslinkers in the polymer chains results in exceptional electrochemical stability for Na metal anodes, leading to a significantly prolonged lifespan even at high current densities, which is at the top of the reported literature. The mechanical properties measurements and electro-chemo-mechanical phase-field model are performed to interpret the impact of the ionic transportation capability (decoupled mechanical) and mechanic property in the metal-doped polymer interface. In addition, this approach provides a promising strategy for the rational design of electrode interfaces, providing enhanced mechanical stability and improved sodiophilicity, which can open up opportunities for the fabrication of next-generation energy storage.

Semaphorin 3A Inhibits Endoplasmic Reticulum Stress Induced by High Glucose in Müller Cells.

PURPOSE: This study aimed to explore the effect of the Semaphorin3A (Sema3A)/Neuropilin-1 (Nrp-1) pathway on Müller cell activities and endoplasmic reticulum (ER) stress induced by high glucose (HG) in vitro. METHODS: The primary Müller cells of C57BL/6J mice were isolated and cultured in normal or high glucose medium. The expression of endogenous Sema3A and its coreceptor Nrp-1 was measured by Western blot. Müller cells were incubated with exogenous recombinant Sema3A protein or transfected with lentiviral vectors expressing small hairpin RNA (shRNA) to knock down the expression of endogenous Sema3A. The proliferation of Müller cells was detected by CCK-8 assay and EdU staining. The migratory ability was detected by the Transwell migration assay. The level of endoplasmic reticulum (ER) stress was analyzed through the detection of GRP78/BiP, IRE1α, phosphorylated IRE1αS724 (p-IRE1αS724), and the splicing rate of XBP1 (XBP1s/XBP1) by using immunofluorescence, Western blot or quantitative polymerase chain reaction (qPCR). RESULTS: HG induced the upregulation of endogenous Sema3A and Nrp-1 receptors in Müller cells. The expression of GRP78/BiP and IRE1α was upregulated by HG, with an increased splicing rate of XBP1. Exogenous Sema3A inhibited HG-induced Müller cell proliferation, migration, and GRP78/BiP-IRE1α-XBP1 axis activation. Knockdown of Sema3A promoted proliferation, migration, and ER stress induced by high glucose in Müller cells. CONCLUSION: Sema3A inhibited the increased proliferative and migratory activities induced by high glucose by attenuating ER stress in Müller cells.

Elevated number and density of macrophage-like cell as a novel inflammation biomarker in diabetic macular edema.

To quantitatively analyze the number and density of macrophage-like cells (MLCs) at the vitreoretinal interface at macular region in diabetic retinopathy (DR) with and without diabetic macular edema (DME). This cross-sectional study involved 240 eyes of 146 treatment-naïve DR patients, including 151 eyes with DME. The number and density of MLCs were analyzed quantitatively using optical coherence tomography angiography (OCTA) and were compared between DME and non-DME eyes as well as proliferative DR (PDR) and non-PDR (NPDR) eyes. Correlation between MLCs density and vessel density of macular superficial capillary plexus (SCP) at macular region was evaluated. The number and density of macular MLCs were both elevated in DME group compared to non-DME group (all p < 0.001). The morphology of MLCs in DME eyes appeared larger and fuller. NPDR eyes had higher number and density of MLCs (p = 0.027 and 0.026), greater central macular thickness (CMT) (p = 0.002) and vessel density than PDR eyes in non-DME group but comparable to PDR eyes in DME group. The number and density of MLCs at macular region were significantly higher with larger and fuller morphology in DR patients with DME than those without DME. PDR eyes had fewer MLCs than NPDR eyes for DR eyes without DME.

From Nanoalloy to Nano-Laminated Interfaces for Highly Stable Alkali-Metal Anodes.

Metal anodes are considered the holy grail for next-generation batteries because of their high gravimetric/volumetric specific capacity and low electrochemical potential. However, several unsolved challenges have impeded their practical applications, such as dendrite growth, interfacial side reactions, dead layer formation, and volume change. An electrochemically, chemically, and mechanically stable artificial solid electrolyte interphase is key to addressing the aforementioned issue with metal anodes. This study demonstrates a new concept of organic and inorganic hybrid interfaces for both Li- and Na-metal anodes. Through tailoring the compositions of the hybrid interfaces, a nanoalloy structure to nano-laminated structure is realized. As a result, the nanoalloy interface (1Al2 O3 -1alucone or 2Al2 O3 -2alucone) presents the most stable electrochemical performances for both Li-and Na-metal anodes. The optimized thicknesses required for the nanoalloy interfaces for Li- and Na-metal anodes are different. A cohesive zone model is applied to interpret the underlying mechanism. Furthermore, the influence of the mechanical stabilities of the different interfaces on the electrochemical performances is investigated experimentally and theoretically. This approach provides a fundamental understanding and establishes the bridge between mechanical properties and electrochemical performance for alkali-metal anodes.

Treatment for Retinopathy of Prematurity in Twins: The Small Twin without High Birth Weight Discordant Is Not at Increased Risk.

Purpose: As common retinopathy is observed in low-birth infants, the characteristics of ROP in twins are worth exploring. The present study tried to demonstrate the risk factors of treatment for retinopathy of prematurity (ROP) in twins both diagnosed with ROP. Methods: A retrospective, institution-based cohort study of 62 premature ROP twin pairs with a mean gestational age (GA) younger than 35 weeks and a birth weight (BW) lower than 2500 g. Only infants with a follow-up period longer than 6 months and complete treatment records were included. The demographic data, treatment requirements and further rescue treatments were all collected and analyzed for all infants according to whether they accepted treatments. Moreover, all twin infants were divided into small and large twin groups according to birth weight, and they were also categorized as three groups according to the treatment requirement including both twins receiving treatment (BT group), one of the twins receiving treatment (ST group) and none of the twins receiving treatment (NT group). Comparisons of demographic data, treatment requirements and further rescue treatments were all conducted according to the different grouping methods. Results: The mean GA of the enrolled infants was (29.29 ± 2.45) weeks with a mean BW of (1335.77 ± 390.36) grams. Among them, 110 infants were mechanically ventilated. Fifty-one of the infants did not receive any treatment and 73 infants received laser or intravitreal injection of anti-VEGF agents. In total, 64 infants only underwent intravitreal injection of anti-VEGF agents or laser treatment, while the other nine infants received scleral buckling or vitrectomy as a necessary treatment when the retinal detachment was observed. No significantly different mechanical ventilation or treatment requirements could be observed between the small twin group and the large twin group (p = 0.73, 0.94). The twins in the BT groups showed the lowest BW, while the NT group infants had the highest BW. The GA for the BT, ST and NT groups were (27.86 ± 1.87) weeks, (29.60 ± 1.52) weeks and (31.33 ± 2.39) weeks, respectively, and showed significant differences as well (p < 0.001). Conclusion: Being a small twin in twin-paired ROP without a high BW discordant will not increase the risk for treatment requirement or additional surgery necessity with a much more severe stage of ROP.

Atypical Adams-Oliver syndrome with typical ocular signs of familial exudative vitreoretinopathy.

AIM: To report an atypical Adams-Oliver syndrome (AOS) family with typical ocular signs of familial exudative vitreoretinopathy (FEVR). METHODS: A patient with visible avascular area and obvious non-perfusion zone in the peripheral retina with systemic signs of AOS was reported. Familial and personal characteristics were collected for the patient and his sister. Gene sequencing and ophthalmic examinations including fluorescein angiography were all performed for the whole family. RESULTS: Two novel mutations of DOCK6 (c.1396C>T and c.4796G>A) were identified in the proband and his family, and two compound heterozygous mutations were revealed in the proband and his sister. The patient and his sister showed physical deformities and mental abnormalities while FEVR mimicking retinal disorder can also be defined. No remarkable ocular or systemic abnormality can be observed for their parents. Peripheral retinal non-perfusion area, obvious abnormal vascularization or even retinal fold were observed in the proband and his sister, while only small avascular zone was identified for their parents. CONCLUSION: This is the first genetic authenticated AOS case mimicked as FEVR with genetic sequencing of a family. For the patients with ocular phenotype of FEVR, further examination should be performed if the systemic or mental abnormalities exist.

Comparison of 24×20 mm2 swept-source OCTA and fluorescein angiography for the evaluation of lesions in diabetic retinopathy.

AIM: To compare ultra-widefield (24×20 mm2) swept-source optical coherence tomography angiography (SS-OCTA) and fluorescein angiography (FA) in the evaluation of diabetic retinopathy (DR) lesions. METHODS: Forty-six eyes of 23 patients with treatment-naïve DR were included at Peking University People's Hospital from September 1, 2021, until December 31, 2021, as well as 23 age and gender matched healthy controls. Quantitative assessments of DR lesions on FA and SS-OCTA (superficial capillary plexus, SCP, 24×20 mm2) were performed. RESULTS: Area of fovea avascular zone (FAZ) was larger in DR cases than controls (0.34±0.069 mm2 vs 0.287±0.108 mm2, P=0.006). In DR eyes, the mean FAZ area was 0.34±0.069 and 0.334±0.087 mm2 on SS-OCTA and FA, respectively (P=0.428), while the median FAZ perimeter was 2.382 (IQR, 2.201-2.59) and 2.333 (IQR, 2.138-2.6) mm on SS-OCTA and FA images (P=0.733). There was no significant difference in the size of the non-perfusion area (NPA) between the images on SS-OCTA and FA (12.389, IQR 4.96-28.3 and 11.125, IQR 5-28.31 mm2, P=0.197). The median total microaneurysm (MA) count was 35 (IQR, 19-46) and 73 (IQR, 43-93) on SS-OCTA and FA (P<0.001), respectively. No significant difference in intra-retinal microvascular abnormality (IRMA) and neovascularization (NV) count was found between the two techniques. The intraclass coefficient (ICCs) of all the parameters above indicated stable repeatability. CONCLUSION: Ultra-widefield SS-OCTA represents a reliable, noninvasive, and quantitative imaging technique in the assessment of microvasculature in DR, which offers a potential substitute for FA in DR evaluation.

An Insertion Variant in CRH Confers an Increased Risk of Central Serous Chorioretinopathy.

Purpose: To identify a novel corticotropin-releasing hormone (CRH) gene variant relevant in patients with central serous chorioretinopathy (CSC). Methods: We performed a genetic study of CSC in families and sporadic cases with controls. Using whole-exome sequencing and linkage analysis, we identified a heterozygous insertion variant, Gln52insPro, in the CRH gene that cosegregated in two Chinese families with CSC. This variant was evaluated among an additional 1307 patients with CSC and 1438 ethnicity-matched control individuals from three independent Chinese cohorts. Results: The CRH variant was strongly associated with CSC in these cohorts of Chinese patients (Pmeta = 1.24 × 10-11; odds ratio, 3.01; 95% confidence interval, 2.15-4.21). The risk variant Gln52insPro decreased CRH gene expression. Conclusions: Our results implicate the hypothalamic-pituitary-adrenal stress response system in the pathogenesis of CSC and provide a novel rationale for therapeutic intervention.

Metabolomic comparison followed by cross-validation of enzyme-linked immunosorbent assay to reveal potential biomarkers of diabetic retinopathy in Chinese with type 2 diabetes.

Purpose: To identify the biomarkers in the critical period of development in diabetic retinopathy (DR) in Chinese with type 2 diabetes using targeted and untargeted metabolomics, and to explore the feasibility of their clinical application. Methods: This case-control study described the differential metabolites between 83 Chinese type 2 diabetes mellitus (T2DM) samples with disease duration ≥ 10 years and 27 controls matched cases. Targeted metabolomics using high-resolution mass spectrometry with liquid chromatography was performed on plasma samples of subjects. The results were compared to our previous untargeted metabolomics study and ELISA was performed to validate the mutual differential metabolites of targeted and untargeted metabolomics on plasma. Multiple linear regression analyses were performed to adjust for the significance of different metabolites between groups. Result: Mean age of the subjects was 66.3 years and mean T2DM duration was 16.5 years. By cross-validating with results from previous untargeted metabolomic assays, we found that L-Citrulline (Cit), indoleacetic acid (IAA), 1-methylhistidine (1-MH), phosphatidylcholines (PCs), hexanoylcarnitine, chenodeoxycholic acid (CDCA) and eicosapentaenoic acid (EPA) were the most distinctive metabolites biomarkers to distinguish the severity of DR for two different metabolomic approaches in our study. We mainly found that samples in the DR stage showed lower serum level of Cit and higher serum level of IAA compared with samples in the T2DM stage, while during the progression of diabetic retinopathy, the serum levels of CDCA and EPA in PDR stage were significantly lower than NPDR stage. Among them, 4 differential key metabolites including Cit, IAA, CDCA and EPA were confirmed with ELISA. Conclusion: This is the first study to compare the results of targeted and untargeted metabolomics via liquid chromatography-mass spectrometry to find the serum biomarkers which could reflect the metabolic variations among different stages of DR in Chinese. The progression of DR in Chinese at different critical stages was related to the serum levels of specific differential metabolites, of which there is a significant correlation between DR progression and increased IAA and decreased Cit, hexanoylcarnitine, CDCA, and EPA. However, larger studies are needed to confirm our results. Based on this study, it could be inferred that the accuracy of targeted metabolomics for metabolite expression in serum is to some extent higher than that of untargeted metabolomics.